PB2312: REACTIVATION OF HEPATITIS B VIRUS FOLLOWING RITUXIMAB IN B LYMPHOID HEMOPATHIES
Authors: Miled Wafa, Dorra Jabeur, Raoudha Mansouri, Malek Sayedi, Karima Kacem, Raihane Ben Lakhal
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Hepatitis B virus (HBV) is major health problem worldwide. Chemotherapy or immunosuppressive therapy in current or previously infected persons with HBV causes HBV reactivation. Patients receiving rituximab are at high risk of HBV reactivation. It can occur within one year after chemotherapy or immunosuppressive therapy. Aims: The aim of our work was to study the incidence of HBV reactivation in patients with B lymphoid hemopathies receiving rituximab and to describe the associated factors. Methods: We performed a retrospective study involving patients with B lymphoid hemopathies, in the clinical hematology department of Aziza Othmana Hospital, in Tunisia between 2013 and 2019. All the patients had a hepatitis B serologic testing at diagnosis and received an immunosuppressive therapy containing rituximab. HBV serologic testing included at least one of the serological markers: HBsAg, Anti HBc, Anti HBs. We adopted the definition of HBV reactivation from international recommendations: it is either a rapid increase in HBV DNA levels by at least 10-100 times in patients with previously detectable HBV viral DNA or a reappearance of HBV viral DNA (>100IU) in individuals who had no viremia before inducing rituximab or HBsAg seroconversion +/- appearance of HBV DNA in initially HBsAg-negative patients before immunosuppression. Results: Two hundred and thirty patients were included. Four cases of HBV reactivation were observed, representing an incidence of 1.7%. The median age was 44 years [31,56] with a sex ratio of 1. Two patients had diffuse large B-cell lymphoma stage IV and stage III, respectively. One patient was being followed for splenic marginal zone lymphoma and one had an active chronic lymphocytic leukemia stage B binet. At the time of diagnosis, all patients had an interpretable serology: two had a non-active chronic hepatitis B profile with an undetectable HBV DNA. One patient was immune due to a natural infection. Viral load was not requested. One patient had a profile of immunity due to vaccination. Consultation with gastroenterologists was requested for the two patients diagnosed with chronic hepatitis B and pre-emptive treatment was started before chemotherapy. All patients received immunosuppressive therapy containing rituximab such as RCHOP, FCR and RCLB. Three patients received a median of 8 cycles of rituximab and a median dose of corticosteroids of 2500mg/m2. The median time to HBV reactivation from the last cycle of rituximab was 447 days [40 days, 3 years]. Two patients were on continuous preemptive treatment at the time of reactivation. All patients presented with acute hepatitis with liver dysfunction, three of whom required hospitalization with a favorable outcome on curative antiviral therapy. At univariate analysis, HBsAg positivity at diagnosis was associated with an increased risk of HBV infection (p=0.001). Summary/Conclusion: HBV reactivation causes significant morbidity and mortality if not diagnosed and managed appropriately. In hematology, we have multiple challenges: patients are exposed to several high-risk drugs for HBV reactivation besides rituximab such as doxorubicin and high-dose corticosteroids. A complete HBV screening at diagnosis is insufficient. Clinicians should be aware of the importance of the pre-emptive strategy based on pre-emptive antiviral treatment and its initiation with strict monitoring of patient compliance. Keywords: Lymphoma, Immunosuppressive therapy